rTMS for the treatment of Alzheimer’s disease: where should we be stimulating?

Heath, Alesha; Taylor, Joy L.; McNerney, M. Windy

doi:10.1080/14737175.2018.1538792

Cited by 18 publications

(14 citation statements)

References 26 publications

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“…None of the studies included in this analysis compared the outcomes associated with stimulation at different sites. Considering the different neurodegenerative and cognitive impairment characteristics of MCI and AD, the ideal location for rTMS stimulation remains unclear (Heath et al, 2018 ). Studies with larger sample sizes are required to determine the best stimulation targets for rTMS that yield optimal cognition improvement.…”

Section: Discussionmentioning

confidence: 99%

Effects of Repetitive Transcranial Magnetic Stimulation in Patients With Mild Cognitive Impairment: A Meta-Analysis of Randomized Controlled Trials

Zhang

Lan

Chen

et al. 2021

Front. Hum. Neurosci.

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Background: Mild cognitive impairment (MCI) is an intermediary state between normal aging and dementia. It has a high risk of progression in patients with Alzheimer's disease (AD). Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation technique used to improve cognitive deficits in patients with MCI and AD. Although previous meta-analyses included studies carried on patients with MCI and AD, few studies have analyzed patients with MCI independently. This meta-analysis aimed to evaluate the effects and safety of rTMS on cognition function in patients with MCI and factors that may influence such effects.Methods: Data used in this study were searched and screened from different databases, including PubMed, Web of Science, Embase, the Cochrane Library, Chinese National Knowledge Infrastructure (CNKI), Chinese Technical Periodicals (VIP), Wanfang Database, and China BioMedical Literature Database (SinoMed). The retrieved studies were carefully reviewed, data were extracted, and the quality of data was assessed.Results: A total of 12 studies involving 329 patients with MCI were included in the present meta-analysis. The analyses results revealed that rTMS improved cognitive function [standardized mean difference (SMD) = 0.83, 95% confidence interval (CI) = 0.44–1.22, p = 0.0009] and memory function (SMD = 0.73, 95% CI = 0.48–0.97, p < 0.00001) in the MCI + rTMS active group when compared to the sham stimulation group. The showed that: (1) cognitive improvement was more pronounced under high-frequency rTMS stimulation of multiple sites, such as the bilateral dorsolateral prefrontal cortex and (2) more than 10 rTMS stimulation sessions produced higher improvement on cognition function in patients with MCI.Conclusions: This study shows that rTMS can improve cognitive function in patients with MCI, especially when applied at high frequency, multi-site, and for a prolonged period. However, further studies are required to validate these findings and explore more effective stimulation protocols and targets.Systematic Review Registration: [http://www.crd.york.ac.uk/PROSPERO/], identifier: CRD 42021238708.

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Section: Discussionmentioning

confidence: 99%

Effects of Repetitive Transcranial Magnetic Stimulation in Patients With Mild Cognitive Impairment: A Meta-Analysis of Randomized Controlled Trials

Zhang

Lan

Chen

et al. 2021

Front. Hum. Neurosci.

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“…Nevertheless, starting from the idea that it induces a gradual readjustment of an intact but “functionally” reduced area due to a steady reduction in synaptic strength, every effort that aims at improving cognition must consider the level of cognitive efficacy and neural activity of the stimulated network. Therefore, NIBS potential should be exploited before the significant neuronal loss has occurred [ 89 ], with a well-characterized sample, a precise definition of the stimulation dose based on individual anatomy [ 90 , 91 ]), and adopting a single-subject approach [ 92 , 93 ]). In addition to this point, the role of individual features, such as demographics (e.g., [ 56 ]) and biological variables [ 70 ], in modulating NIBS efficacy is yet to be explored.…”

Section: Discussionmentioning

confidence: 99%

Protocols for cognitive enhancement. A user manual for Brain Health Services—part 5 of 6

et al. 2021

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Cognitive complaints in the absence of objective cognitive impairment, observed in patients with subjective cognitive decline (SCD), are common in old age. The first step to postpone cognitive decline is to use techniques known to improve cognition, i.e., cognitive enhancement techniques.We aimed to provide clinical recommendations to improve cognitive performance in cognitively unimpaired individuals, by using cognitive, mental, or physical training (CMPT), non-invasive brain stimulations (NIBS), drugs, or nutrients. We made a systematic review of CMPT studies based on the GRADE method rating the strength of evidence.CMPT have clinically relevant effects on cognitive and non-cognitive outcomes. The quality of evidence supporting the improvement of outcomes following a CMPT was high for metamemory; moderate for executive functions, attention, global cognition, and generalization in daily life; and low for objective memory, subjective memory, motivation, mood, and quality of life, as well as a transfer to other cognitive functions. Regarding specific interventions, CMPT based on repeated practice (e.g., video games or mindfulness, but not physical training) improved attention and executive functions significantly, while CMPT based on strategic learning significantly improved objective memory.We found encouraging evidence supporting the potential effect of NIBS in improving memory performance, and reducing the perception of self-perceived memory decline in SCD. Yet, the high heterogeneity of stimulation protocols in the different studies prevent the issuing of clear-cut recommendations for implementation in a clinical setting. No conclusive argument was found to recommend any of the main pharmacological cognitive enhancement drugs (“smart drugs”, acetylcholinesterase inhibitors, memantine, antidepressant) or herbal extracts (Panax ginseng, Gingko biloba, and Bacopa monnieri) in people without cognitive impairment.Altogether, this systematic review provides evidence for CMPT to improve cognition, encouraging results for NIBS although more studies are needed, while it does not support the use of drugs or nutrients.

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“…Even though up to date no specific area has been identified as ideal to provide the most beneficial effects, it is suggested that several areas or pathways that are known to be negatively affected in AD, could provide potential targets. On that basis, by targeting these areas, crucial for normal cognitive function brain connections and pathways could be strengthened or rescued (e.g., stimulating the precuneus to alleviate abnormal functional connectivity in the default mode network) leading to cognitive improvements ( Heath et al, 2018 ).…”

Section: Gamma Frequency Non-invasive Brain Stimulation In Alzheimer’s Disease Patientsmentioning

confidence: 99%

Gamma Oscillations in Alzheimer’s Disease and Their Potential Therapeutic Role

Traikapi

Konstantinou

2021

Front. Syst. Neurosci.

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Despite decades of research, Alzheimer’s Disease (AD) remains a lethal neurodegenerative disorder for which there are no effective treatments. This review examines the latest evidence of a novel and newly introduced perspective, which focuses on the restoration of gamma oscillations and investigates their potential role in the treatment of AD. Gamma brain activity (∼25–100 Hz) has been well-known for its role in cognitive function, including memory, and it is fundamental for healthy brain activity and intra-brain communication. Aberrant gamma oscillations have been observed in both mice AD models and human AD patients. A recent line of work demonstrated that gamma entrainment, through auditory and visual sensory stimulation, can effectively attenuate AD pathology and improve cognitive function in mice models of the disease. The first evidence from AD patients indicate that gamma entrainment therapy can reduce loss of functional connectivity and brain atrophy, improve cognitive function, and ameliorate several pathological markers of the disease. Even though research is still in its infancy, evidence suggests that gamma-based therapy may have a disease-modifying effect and has signified a new and promising era in AD research.

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rTMS for the treatment of Alzheimer’s disease: where should we be stimulating?

Cited by 18 publications

References 26 publications

Effects of Repetitive Transcranial Magnetic Stimulation in Patients With Mild Cognitive Impairment: A Meta-Analysis of Randomized Controlled Trials

Effects of Repetitive Transcranial Magnetic Stimulation in Patients With Mild Cognitive Impairment: A Meta-Analysis of Randomized Controlled Trials

Protocols for cognitive enhancement. A user manual for Brain Health Services—part 5 of 6

Gamma Oscillations in Alzheimer’s Disease and Their Potential Therapeutic Role

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